Gaucher disease is an autosomal recessive disease caused by severely decreased intracellular hydrolysis of glucosylceramides and other glucosphingolipids. Nearly all cases are due to heritable deficiency of lysosomal glucocerebrosidase (GC) deficiency which causes massive accumulation of macrophages containing unhydrolyzed glucosylceramides and other glucosphingolipids in the liver, spleen, bone marrow cells and other monocyte/macrophage-derived cells. Most patients with GC deficiency are treated with injectable forms of human GC. This therapy results in remarkable decreases in storage in liver and spleen, but signs and symptoms relating to bone, including bone pain and osteopenia only occur after years of therapy for improvement or else have been refractory. However, numerous clinical trials and a recent Technology Assessment Conference sponsored by NIDDK have recognized that successful treatment of chronic debilitating skeletal complications of Gaucher disease will require alternatives and/or adjunctive intervention. The purpose of this project is to determine whether the osteopenia that is seen in most adults with Gaucher disease can be corrected by antiresorptive adjunctive therapy in patients with Gaucher disease who are receiving enzyme therapy. To do so, we will perform a 3-year, double-blind, two-arm controlled trial of alendronate, 40 mg/day on adults with Gaucher disease who have been treated at least 24 months with enzyme therapy prior to entry into the study. Eighty-two such patients from two major Gaucher Treatment Centers will be randomized into two groups, which will receive enzyme therapy (8-60 U/kg/q 2 weeks) with alendronate or with placebo for 24 months. Therapeutic outcome will be monitored by measurement of bone density at the lumbar spine and scoring of skeletal x-rays for disease severity at the time of entry into the study, and at 6-month intervals until the end of the study. The successful outcome of these studies may lead to new therapeutic regimens for Gaucher disease that control or reverse osteopenia, and may lead to reduction of dosage in costly enzyme therapy.